Clinical Pregnancy In Women Research Articles

Enhancing predictions of embryo implantation in thin endometrium: a comparative analysis of endometrial thickness in frozen versus fresh IVF cycles

This study investigated whether the difference between endometrial thickness in the frozen embryo transfer (FET) cycle and the preceding fresh stimulated cycle predicts clinical pregnancy in women with thin endometrium. A retrospective analysis of 335 cycles in 227 women (age < 43) with endometrium < 8 mm in the FET cycle was conducted. Endometrial thickness was assessed using the ratio (ETfrozen/fresh) and absolute difference (ETfresh-frozen) between the maximal endometrial thickness measured during the stimulated IVF cycle and that measured in the FET cycle. We hypothesized that a smaller difference and higher ratio during FET will be associated with higher pregnancy rate. No embryo implantation occurred in women with an FET endometrial thickness < 5.9 mm and an ETfrozen/fresh < 0.86. Cycles with a positive beta-human chorionic gonadotropin (ß-hCG) showed a significantly lower mean ETfresh-frozen (1.89 ± 1.78 vs 2.30 ± 1.81, p = 0.03), and a significantly higher ETfrozen/fresh ratio (0.82 ± 0.17 vs. 0.77 ± 0.15, p = 0.024). Endometrial thickness in the FET cycle normalized to the preceding stimulated cycle is associated with implantation and may constitute a novel predictor of FET success in women with thin endometrium.

P-727 The impact of antidepressants and anxiolytics on assisted reproductive technology treatment outcomes

Abstract Study question Does antidepressant and anxiolytic use impact the chance of live birth after assisted reproductive technology (ART) treatment? Summary answer For women using antidepressants, ART treatment is as successful as for others. However, concomitant anxiolytic use was associated with failure to succeed. What is known already Infertility and depression are prevalent disorders in women of reproductive age and may occur coincidently. Antidepressants constitute the mainstay in treatment for moderate-severe depression, and selective serotonin reuptake inhibitors (SSRIs) are among the most commonly used antidepressants because they, in general, cause few side effects. However, antidepressant use in women undergoing ART treatment may be considered to balance the possible risks of untreated depression against fetal drug exposure and the efficacy of ART treatment. Furthermore, up to 50% of patients with depression also meet the criteria for anxiety disorders and may be treated with anxiolytics. Study design, size, duration This is an observational cohort study based on the Danish health registries. The use of antidepressants, i.e. as current or recent users, and anxiolytics or hypnotics at embryo transfer was obtained from the prescription register and information on all ART treatments and childbirths between 2006 and 2019 from the Danish ART register and the Danish birth register. Participants/materials, setting, methods The study population included 130,170 embryo transfers in 48,156 women undergoing ART treatment. A total of 1505 women were exposed to antidepressants at the time of embryo transfer, and 1160 women were recent users who discontinued before embryo transfer. We used mixed-effects logistic regression analyses. The association between antidepressants and anxiolytics respectively and ART was analyzed taking potential confounders into account estimating the odds ratios(OR) of either a biochemical pregnancy, clinical pregnancy, or live birth. Main results and the role of chance The adjusted OR(aOR) and corresponding 95% confidence interval (CI) of a biochemical-, and clinical pregnancy in women with current use of antidepressants at time of embryo transfer were 0.87 (95% CI: 0.73-1.04) and 0.84 (95% CI: 0.57-1.20), respectively, and 0.90 (95% CI: 0.67-1.19) for live birth. For women who discontinued antidepressant use before embryo transfer (labeled recent users), the aORs for a biochemical-, clinical pregnancy and live birth were 0.95 (95% CI: 0.76-1.17), 0.71 (95% CI: 0.46-1.09) and 1.02 (95% CI: 0.72-1.45), respectively. When analyzing women who use or recently used antidepressants in combination with anxiolytics or hypnotics the chance of a live birth was decreased markedly with an aOR of 0.15 (95% CI: 0.04-0.51). Based on nationwide data from more than a decade of ART treatments, we found that the use of antidepressants at the time of embryo transfer was not associated with a decreased chance of biochemical or clinical pregnancy, or live birth. However, when women treated with antidepressants also used anxiolytics or hypnotics, the chance of a live birth was significantly decreased though based on a limited number of patients suggesting a point of further investigation and attention. Limitations, reasons for caution As in all observational studies, it can never be ensured that the patients take the medicine, but we used information on prescriptions for antidepressants/anxiolytics from the prescription register using at least two redeemed prescriptions within 182 days before, and until 182 days after the date of embryo transfer. Wider implications of the findings Use of antidepressants at the time of embryo transfer was not associated with a decreased chance of biochemical or clinical pregnancy, or live birth. However, when antidepressants are used concomitantly with anxiolytics or hypnotics, the chance of live birth is significantly decreased suggesting the need for further investigation and attention. Trial registration number The study was funded by The Region of Southern Denmark and Merck.

Nomogram to predict the probability of clinical pregnancy in women with poor ovarian response undergoing in vitro fertilization/ intracytoplasmic sperm injection cycles.

Poor ovarian response (POR) is associated with decreased clinical pregnancy rates, emphasizing the need for developing clinical prediction models. Such models can improve prognostic accuracy, personalize medical interventions, and ultimately enhance live birth rates among patients with POR. This study aims to develop and validate a prognostic model for predicting clinical pregnancy outcomes in individuals with POR undergoing in vitro fertilization/ intracytoplasmic sperm injection (IVF/ICSI) cycles. A retrospective cohort of 969 patients with POR undergoing fresh embryo transfer cycles at the Reproductive Center of Fujian Maternal and Child Health Center from January 2018 to January 2022 was included. The cohort was randomly divided into model (n = 678) and validation (n = 291) groups in a 7:3 ratio. A single-factor analysis was performed on the model group to identify variables influencing clinical pregnancy. Optimal variables were selected using LASSO regression, and a clinical prediction model was constructed using multivariate logistic regression analysis. The model's calibration and discrimination were assessed using receiver operating characteristic (ROC) and calibration curves, while the clinical utility was evaluated using decision curve analysis. Multivariate logistic regression analysis revealed that the age of the women (odds ratio [OR] 0.936, 95% confidence interval [CI] 0.898-0.976, P = 0.002), body mass index (BMI) ≤ 24 (OR 2.748, 95% CI 1.724-4.492, P < 0.001), antral follicle count (AFC) (OR 1.232, 95% CI 1.073-1.416, P = 0.003), anti-Müllerian hormone (AMH) (OR 1.67, 95% CI 1.178-2.376, P = 0.004), number of mature oocytes (OR 1.227, 95% CI 1.075-1.403, P = 0.003), number of embryos transferred (OR 1.692, 95% CI 1.132-2.545, P = 0.011), and transfer of high-quality embryos (OR 3.452, 95% CI 1.548-8.842, P = 0.005) were independent predictors of clinical pregnancy in patients with POR. According to the receiver operating characteristic (ROC) analysis, the prediction model exhibited an area under the curve (AUC) of 0.752 (0.714, 0.789) in the model group and 0.765 (0.708, 0.821) in the validation group. The clinical decision curve demonstrated that the model held maximum clinical utility in both cohorts when the threshold probability of clinical pregnancy ranged from 6-81% to 12-82%, respectively. Clinical pregnancy outcomes in patients with POR who underwent IVF/ICSI treatment were influenced by several independent factors, including the age of the women, BMI, AFC, AMH, number of mature oocytes, number of embryos transferred, and transfer of high-quality embryos. A clinical prediction model based on these factors exhibited favorable clinical predictive and applicative value. Therefore, this model can serve as a valuable tool for clinical prognosis, intervention, and facilitating personalized medical treatment.

Effects of letrozole alone or in combination with gonadotropins on ovulation induction and clinical pregnancy in women with polycystic ovarian syndrome: a systematic review and meta-analysis of randomized controlled trials.

To compare letrozole in combination with gonadotropins versus letrozole monotherapy in ovulation induction and clinical pregnancy among infertile women with polycystic ovarian syndrome (PCOS). Several databases were searched for available clinical trials from inception until March 2023. We selected randomized controlled trials (RCTs) that compared sequential letrozole/gonadotropin versus letrozole alone among infertile women who met the Rotterdam criteria for PCOS. RevMan software was used to perform our meta-analysis. Our primary outcomes were ovulation and clinical pregnancy rates. Our secondary outcomes were endometrial thickness, number of mature follicles (diameter ≥ 18 mm), and incidence of miscarriage and ovarian hyperstimulation syndrome (OHSS). Six RCTs were retrieved with a total number of 723 patients. The ovulation and clinical pregnancy rates were significantly higher among the letrozole/gonadotropin group versus the letrozole monotherapy group (p < 0.001). In addition, there were significant improvements in endometrial thickness and number of mature follicles in the letrozole/gonadotropin group. There were no significant differences between the two groups regarding incidence of miscarriage and ovarian hyperstimulation syndrome. Letrozole in combination with gonadotropin is superior to letrozole alone in improving ovulation induction and clinical pregnancy among PCOS patients. More trials are required to confirm our findings.

A novel machine learning model for predicting clinical pregnancy after laparoscopic tubal anastomosis

Abstract Background Laparoscopic tubal anastomosis (LTA) is a treatment for women who require reproduction after ligation, and there are no reliable prediction models or clinically useful tools for predicting clinical pregnancy in women who receive this procedure. The prediction model we developed aims to predict the individual probability of clinical pregnancy in women after receiving LTA. Methods Retrospective analysis of clinical data of patients undergoing LAT in the Second Hospital of Lanzhou University from July 2017 to December 2021. Least absolute shrinkage and selection operator (LASSO) regression was used for data dimension reduction and feature selection. We incorporated the patients’ basic characteristics, preoperative laboratory tests and laparoscopic tubal anastomosis procedure signature and obtained a nomogram. The model performance was evaluated in terms of its calibration, discrimination, and clinical applicability. The prediction model was further internally validated using 200 bootstrap resamplings. Results A total of 95 patients were selected to build the predictive model for clinical pregnancy after LTA. The LASSO method identified age, intrauterine polyps, pelvic adhesion and thyroid stimulating hormone(TSH) as independent predictors of the clinical pregnancy rate. The prediction nomogram included the abovementioned four predictive parameters. The model showed good discrimination with an area under the curve (AUC) value of 0.752. The Hosmer‒Lemeshow test of calibration showed that χ2 was 4.955 and the p value was 0.838, which indicates a satisfactory goodness-of-fit. Decision curve analysis demonstrated that the nomogram was clinically useful. Internal validation shows that the predictive model performs well. Conclusion This study presents a nomogram incorporating age, intrauterine polyps, pelvic adhesion and TSH based on the LASSO regression model, which can be conveniently used to facilitate the individualized prediction of clinical pregnancy in women after LTA.

Elevated follicular cortisone level is a negative predictor of clinical pregnancy in women undergoing fresh embryo transfer

BackgroundAlthough numerous studies have investigated the potential correlation between follicular fluid (FF) steroid concentrations and in vitro fertilization/intracytoplasmic sperm injection (IVF/ICSI) outcomes, few have accounted for the effect of controlled ovarian hyperstimulation regimes on FF steroid concentrations. ObjectiveTo comprehensively compare follicular steroid concentrations between women stimulated with gonadotropin-releasing hormone agonist (GnRHa) and antagonist (GnRHant) protocols and to explore the associations between FF steroid concentrations and IVF/ICSI outcomes. MethodsA total of 295 infertile women undergoing IVF/ICSI from January 2018 to May 2020 were enrolled. Eighty-four and 211 women received GnRHa and GnRHant protocols, respectively. Seventeen steroids in FF were quantified by liquid chromatography tandem mass spectrometry (LC–MS/MS), and the correlation of follicular steroids with clinical pregnancy was explored. ResultsFollicular steroid concentrations were similar between the GnRHa and GnRHant groups. Follicular cortisone levels were adversely associated with clinical pregnancy in fresh embryo transfers. Receiver operating characteristic (ROC) analysis revealed an area under the ROC curve (AUC) of 0.639 (95% confidence interval = 0.527–0.751, p = 0.025) for predicting non-pregnancy, with an optimal cutoff value of 15.81 ng/mL (sensitivity = 33.3%, specificity = 94.1%). Women with FF cortisone concentrations ≥15.81 ng/mL were fifty times less likely to achieve clinical pregnancy in fresh embryo transfers than those with FF cortisone levels below this threshold (adjusted OR = 0.019, 95% confidence interval = 0.002–0.207, p = 0.001) after adjusting for age, body mass index, baseline serum progesterone levels, serum levels of luteinizing hormone, estradiol and progesterone on human chorionic gonadotropin day, ovarian stimulation protocols, and the number of transferred embryos. ConclusionsThere was no significant difference in intrafollicular steroid levels between GnRHa and GnRHant protocols, and intrafollicular cortisone level ≥15.81 ng/mL was found to be a strong negative predictor of clinical pregnancy in fresh embryo transfers with high specificity.

P-314 Quantitative analysis of uterine peristalsis using optical flow for motion quantification

Abstract Study question Do women with adenomyosis have altered uterine peristalsis? Summary answer Women with adenomyosis have altered uterine peristalsis on transvaginal sonography (TVS), as measured using optical flow for motion quantification. What is known already Adenomyosis can reduce the chance of clinical pregnancy in women undergoing assisted conception, with altered uterine peristalsis proposed as a mechanism. Uterine peristalsis can be visualised by TVS and is thought to play an important role in sperm transport and embryo implantation. Ultrastructural myometrial abnormalities in adenomyosis cause a disturbance in normal myocyte contractility with subsequent loss of normal rhythmic contraction. We aimed to develop an objective tool to quantify uterine peristalsis on TVS using an algorithm based on optical flow for wave motion quantification in women with adenomyosis. Study design, size, duration Prospective observational cohort study, July - December 2021, of women with moderate/severe adenomyosis (n = 16) and a normal pelvis (n = 21), having TVS during assisted conception. TVS was performed in the mid-sagittal plane for 4 minutes at baseline (BL), day 6-12 of ovarian stimulation (OS) and day of embryo transfer (ET). Recordings were stored offline for analysis using 3D Slicer (Ver. 4.11) and sampled at constant intervals to achieve a set of frames for optical flow analysis. Participants/materials, setting, methods We recruited women with moderate/severe adenomyosis or normal uterus on TVS. Optical flow was used to track pixels over successive TVS frames. Pixel-level displacements for points at endometrial-myometrial junction were used to compute time-period(inverse of frequency, 1/f) and amplitude(u) by fitting to the 2D-wave equation. Fit error was taken as a measure of coordination of wave at endometrial-myometrial junction(uterine peristalsis - up). Myometrial zone standard deviation quantifies spread, a measure of coordination of myometrial contractility(mc). Main results and the role of chance The observed wave of uterine peristalsis (up) at the endometrial-myometrial junction in women with adenomyosis showed a significantly poorer fit with the ideal wave equation compared to women with a normal uterus at all time points (BL (+ 0.725), OS (+ 0.612) and ET (+ 0.627) (n = 37, p &amp;lt; 0.001)), indicating lower coordination of uterine peristalsis in women with adenomyosis compared to women with a normal uterus. Coordination of myometrial contractility was also significantly lower in women with adenomyosis compared to women with a normal uterus at all time points (BL (+ 0.656) , OS (+ 0.510) and ET (+ 0.639) (n = 37, p &amp;lt; 0.001). Statistically significant difference was not found in wave amplitude or frequency between groups (p &amp;gt; 0.06 for both). Limitations, reasons for caution Optical flow for motion quantification has been used here to quantify uterine peristalsis in women with adenomyosis and women with a normal uterus and would require validation prior to use in other uterine pathology. Wider implications of the findings Women with adenomyosis have altered uterine peristalsis and myometrial contractility, which may account for their reduction in chances of conception. The proposed approach for wave motion quantification is an objective tool to quantify uterine peristalsis, with potential for wide clinical application in the gynaecology and assisted conception setting. Trial registration number Not applicable

4D-HyCoSy performed in a reproductive center: retrospective analysis of pain perception, complications and spontaneous pregnancy rate after the technique.

Nowadays 4D hysterosalpingocontrast sonography (4D-HyCoSy) represents a primary technique in the evaluation of tubal impairment, with a low rate of pain referred and complications related, but its role in increasing the chance of spontaneous clinical pregnancy in women in childbearing age is still debated. Retrospective study of 359 women performed 4D-HyCoSy at Reproductive Physiopathology and Andrology Unit, Sandro Pertini Hospital, Rome, during the period 2018-2020. women attending our IVF (in vitro fertilization) center with at least 1 year of infertility. female age over 43 years, previously known severe tubal infertility, suspected anovulation, and semen abnormalities. evaluation of tubal patency, complications related to technique, and pain perception evaluated thanks to a 10-cm visual analogue scale (VAS) Scale. clinical pregnancy rate (PR) after the technique confronted between the group of women with bilateral tubal patency (group A) with the group of monolateral tubal patency (group B) within 30 days and between 30-180 days, and 180 days-1 year from the exam. Time to pregnancy (TTP) and other obstetrical outcomes were evaluated too. The average age of the study's population was 33.3 years. Mean duration of infertility was 2.1 years. Complication rate was 6.4%, and in any case the use of ephedrine was required. 182 (50.6%) women reported absence of pain during the exam (VAS scale value 0) and 131 (36.5%), reported mild pain experience (VAS scale value between 1-4). Spontaneous pregnancy rate was of 29.3% in group A and 30.3% in group B; time to pregnancy was 32 ± 14.7 days in group A and 35 ± 13.1 days in group B. The insurgence of a spontaneous pregnancy was significantly lower for both 4D-HyCosy sub-groups after 30 days following technique respect to 30-180 days and 180 days-1 year following the technique (both p-value < 0.001). We confirm that 4D-HyCoSy is a safe and user-friendly technique, used as first line assessment of tubal patency of women afferent to a reproductive center. We also reported a positive impact on spontaneous pregnancy rate in women performing 4D-HyCoSy, emphasized within the first following month. This mandatory technique for tubal investigation, has not only a function in the diagnostic assessment of female infertility, but also has a therapeutic role, in young women who desire a pregnancy, avoiding, in some cases, the need of IVF treatments and clinical risks linked, while saving medical and monetary resources.

The Value of Anti-Müllerian Hormone in the Prediction of Spontaneous Pregnancy: A Systematic Review and Meta-Analysis.

ObjectiveTo determine whether serum anti-Müllerian hormone (AMH) level is a predictor of clinical pregnancy in women trying to achieve a natural conception.MethodsThe PubMed, Embase, and Cochrane Library databases were searched for articles published until August 2020. Studies that met the inclusion and exclusion criteria were included in the meta-analysis; no language limitations were imposed. Quality was appraised using the Quality Assessment of Diagnostic Accuracy Studies-2 checklist. Heterogeneity due to the threshold effect was identified; thus, we plotted a summary receiver operating characteristic curve and calculated its area under the summary receiver operating characteristic curve (AUC) and Cochran’s Q index to assess whether AMH level is a predictor of spontaneous pregnancy. Publication bias and sensitivity were also assessed.ResultsEleven studies (4,388 women) were ultimately included in this meta-analysis. The AUC and Cochran’s Q indices were 0.5932 and 0.5702, respectively. For women younger than 35 years, the AUC was 0.6355 and the Q index was 0.6025. For those older than 35 years, the AUC was 0.5536 and the Q index was 0.5403. Subgroup analyses by study type and population characteristics showed results similar to the overall outcome. No publication bias was identified, and the sensitivity analysis confirmed the robustness of the final result.ConclusionsSerum AMH levels have poor predictive value for natural pregnancy. The predictive value of AMH was poor in the younger and older subgroups. Our findings suggest that low serum AMH levels are not associated with reduced fertility.IntroductionThis study investigated the predictive value of anti-Müllerian hormone (AMH) level for natural pregnancy. Other than age, few factors can predict the chances of natural fertility. AMH is an established biomarker of ovarian reserve that is widely used to predict oocyte yield in cases of in vitro fertilization (IVF) and menopause. In clinical practice, the applications of AMH are increasing. However, its predictive value for natural conception remains controversial. In this study, since AMH is closely related with ovarian reserve, we evaluated whether it has predictive value for natural pregnancy. Our findings will fine-tune the clinical application of AMH in pre-pregnancy counseling. The topic should be of wide interest to investigators in the reproductive endocrinology and gynecology fields.Systematic Review RegistrationPROSPERO 2020 CRD42020216265, Available from: https://www.crd.york.ac.uk/prospero/display_record.php?ID=CRD42020216265.

P–278 The embryo score provided by the KIDScoreD5 is correlated with implantation rate and clinical outcomes in fresh transfer

Abstract Study question Can the algorithm used by EmbryoScopePlus software predict implantation and clinical pregnancy in women of different age groups on fresh transfer? Summary answer The embryo score generated by KIDScoreD5 is highly related to the rates of implantation and clinical pregnancy in fresh transfers in women of different age. What is known already Artificial Intelligence algorithms use statistics to find patterns in large amounts of data and describe a non-biased approach to multiparameter analysis. Several algorithms have been described, but none has been adopted for universal use. KIDScoreD5 is the algorithm included in the EmbryoScopePlus system and classifies embryos according to the cleavage times and morphology of the blastocyst. Version 3, more current, includes the annotations of the number of pronuclei, the time of division for 2, 3, 4 and 5 cells, time to start of blastulation, and morphology of the Internal Cell Mass and trophectoderm. Study design, size, duration Retrospective study evaluated 86 embryos from January to December 2019 at the Reproferty clinic, grown at EmbryoScopePlus and transferred fresh on the fifth day of embryo development. The morphological and morphokinetic parameters were automatically evaluated by the software and in case of any mistake, they were manually corrected. The embryos were evaluated by KIDScoreD5 v3 in different scores from 0.0 to 9.9 and divided into 4 groups (0.0–2.5; 2.6–5.0; 5.1–7.5; 7.6 –9.9). Participants/materials, setting, methods The inclusion criterion was transfer of a single embryo with 1 gestational sac and positive FHB and transfer of two embryos with 2 gestational sac and positive FHB. Patients with progesterone on the trigger day ≥ 1.5ng/mL and/or with endometrium ≤7mm were excluded. The implantation and clinical pregnancy rates were calculated according to age group, G1: ≤35 years; G2: between 36 and 39 years old; G3: ≥40 years, within the embryo classification. Main results and the role of chance For patients in group 1 (n = 31 embryos), 33.4% of the embryos were classified between 2.6–5.0; 69.20% of embryos with scores between 5.1–7.5 and 57.10% of embryos with scores between 7.6–9.9, with 100% of embryos that implanted, regardless of classification, resulting in clinical pregnancy . For group 2 (n = 35 embryos), they only showed an implantation rate for embryos where the scores were 5.1–7.5 (33.4%) and 7.6 - 9.9 (71.4%) , with 100% being the clinical pregnancy rate in these groups. For patients in group 3 (n = 24 embryos), we also observed implantation only in groups of embryos with a score of 5.1–7.5 (37.5%) and 7.6–9.9 (18.5%) , but the clinical pregnancy rate was lower when compared to the other age groups of the patients, with 33.5% for embryos having a score between 5.1–7.5 and 50% for the group 7.6–9.9. Regarding the average score given by the classification of KIDScore Day 5 v. 3 for embryos that implanted, for patients aged 35 years or less, the average was 6.92; for patients between 36 and 39 years old, the average was 8.06 and for patients aged 40 years or older, the average was 7.32. Limitations, reasons for caution This project is limited because it is a retrospective study and evaluated embryos from a single breeding center. Multicenter and prospective studies are necessary to validate the universal use of the KIDScoreD5 v3 algorithm in time-lapse incubators. Wider implications of the findings: The study showed the ability of KIDScoreD5 v3 to assist the embryologist in deciding which embryo to transfer fresh, according to the patient’s age, in addition to the software being effective in automatic annotation of morphological and morphokinetic parameters. Validating an algorithm universally will improve embryonic selection. Trial registration number Not applicable

O-230 RCT comparing Recombinant-hcg trigger with Dual-trigger (GnRH-agonist and recombinant-hcg ) in improving clinical outcome in ICSI cycles in women with Diminished Ovarian Reserve

Abstract Study question Does use of Dual-trigger (GnRH-agonist with recombinant-hcg) improve the clinical outcome in women with diminished ovarian reserve as compared to Recombinant-hcg trigger? Summary answer Yes, the use of Dual-trigger (GnRH-agonist with recombinant-hcg) improve the clinical outcome in women with diminished ovarian reserve as compared to Recombinant-hcg trigger. What is known already The population of poor responders has grown exponentially over the years and their management of ovarian stimulation remains one of the most challenging aspects. In GnRH antagonist down-regulated IVF-ICSI cycles, dual triggering for the final oocyte maturation with GnRH-a and a reduced dose of hCG improves the rate of fertilization and clinical pregnancy in women with diminished ovarian reserve. Further more, the benefit of lowered cycle cancellation rate would also enable greater percentage of patients with diminished ovarian reserve to reach the final stage of their ART treatment, thereby enhancing their chances of achieving a successful pregnancy . Study design, size, duration This RCT included GnRH antagonist ICSI cycles from 2018-2019. 82 women with diminished ovarian reserve (AMH ≤ 1.1 ng/ml and AFC ≤5) were included. The primary outcome measured was the oocyte fertilization rate, implantation rate and clinical pregnancy rate per oocyte retrieval cycle. Secondary outcome measured was embryo transfer cancellation rate and abortion rate per oocyte retrieval cycle. Participants/materials, setting, methods 82 women with diminished ovarian reserve undergoing fresh embryo transfer were included and randomly divided in two groups - Group-A (hCG trigger/control group: n = 41); and Group-B (dual trigger/study group: n = 41). Both patient groups underwent controlled ovarian stimulation using antagonist. The final oocyte maturation was triggered either by recombinant hCG (Group-A) or by a combination of recombinant hCG and GnRH-agonist (Dual trigger) (Group-B). Main results and the role of chance The dual-trigger group had significantly higher fertilization rate (62.8 vs. 37.6%), higher clinical pregnancy rate (31.4% vs. 18.1%) as compared to the recombinant-hCG trigger group. In addition, the abortion rate(12.1% vs. 21.3%) and embryo transfer cancellation rate (8.3% vs. 16.1%) were both significantly lower in the dual trigger group. The baseline characteristics for the control and the study group were similar and there was no significant difference in the patient age, serum AMH level, and cause of infertility. The total r-FSH dose, duration of stimulation, endometrial thickness, and serum hormone profile on the day of trigger were also similar between the control and the study group. The main advantage of triggering with GnRH-a is that it induces a mid-cycle FSH surge which resembles the natural ovulatory cycle hormonal changes. Study shows that in GnRH antagonist ART cycles, dual triggering with GnRH-a and hCG could significantly improve the rate of fertilization and clinical pregnancy in diminished ovarian reserve women. Furthermore, the benefit of lowered cycle cancellation rate would also enable greater percentage of patients with diminished ovarian reserve to reach the final stage of their ART treatment thereby enhancing their chance of achieving a successful pregnancy as well as reducing their mental stress. Limitations, reasons for caution The main limitation of our study is the low patient number. Triggering with GnRH-a has become a significant part of contemporary ART practice, especially in high responders, oocytes donors and oncology patients. However, more RCTs are required in order to justify the use of GnRH-agonists in poor responders in ART cycles. Wider implications of the findings Results of our study concurred with other studies of dual triggering, calls for a possible paradigm shift in ovulation-triggering agent for GnRH-antagonist cycles. Diminished ovarian reserve patients are constituting a large part of clinical ART practice and for such patients, obtaining maximum mature oocytes and good embryos is vitally important. Trial registration number not applicable

P–585 The influence of omega–3 fatty acids on female fertility in assisted reproductive technology

Abstract Study question Is there evidence that the intake of omega–3 fatty acids has a positive effect on probability of clinical pregnancy in women undergoing IVF/ICSI treatment? Summary answer No significant correlation was found between omega- 3 fatty acid intake (neither supplemental or as fish intake) and clinical pregnancy. What is known already: Omega–3 fatty acids are important substrates in metabolism and the supplement of omega–3 fatty acids have been thought to have a positive effect on semen quality in infertile men. Studies have shown that the intake of omega–3 fatty acids might also have a direct effect on oocytes, the quality of the embryos, and implantation of the embryo in the uterus at conception. However, the role of omega–3 fatty acids in female fertility still remains unclear as the relationship between omega–3 fatty acids and successful IVF treatment in women has shown conflicting results. Study design, size, duration Systematic review. Systematic literature research (PRISMA) on PubMed, Embase, and Cochrane identifying clinical studies focusing on omega–3 fatty acid intake amongst women receiving IVF treatment, using good scientific practice for literature search and management. 5 articles meeting inclusion criteria were found, with a total of 1.100 women undergoing IVF/ICSI treatment. Participants/materials, setting, methods: Population: women in fertility treatment Intervention: omega–3 fatty acid and/or fish intake Comparison: No/low intake of omega–3 fatty acid and/or fish intake Outcome: Primary: clinical pregnancy rate, Secondary: number of follicles, embryo quality, live birth rate Main results and the role of chance Number of follicles was found to be inversely associated to omega–3 intake in a single study. Higher levels of total omega–3 intake were found to be positively associated to embryo morphology scores, and thus quality, independent on energy intake. None of the four studies considering clinical pregnancy found any statistical significance in the association between fish intake and clinical pregnancy. Regarding live birth as an endpoint, fish intake, but not fish oil supplements, was seen to significantly increase the probability in one study with a dose-response relationship. A similar association was not found by the only other study also examining live birth. Limitations, reasons for caution: Only five studies were found to meet inclusion criteria. None of the included studies were randomized controlled trials. No meta-analysis was carried out due to the heterogeneity of the studies. Wider implications of the findings: The need for further studies, including randomized controlled trials of high quality with larger population sizes, is critical in order to thoroughly investigate and conclude any possible association of the beneficial effect of omega–3 fatty acids on female fertility in regard to IVF treatment. Trial registration number Not applicable

Endometrial injury in women undergoing in vitro fertilisation (IVF).

Implantation of an embryo within the endometrial cavity is a critical step in the process of in vitro fertilisation (IVF). Previous research has suggested that endometrial injury (also known as endometrial scratching), defined as intentional damage to the endometrium, can increase the chance of pregnancy in women undergoing IVF. To assess the effectiveness and safety of endometrial injury performed before embryo transfer in women undergoing in vitro fertilisation (IVF) including intracytoplasmic sperm injection (ICSI) and frozen embryo transfer. In June 2020 we searched the Cochrane Gynaecology and Fertility Group Specialised Register, CENTRAL, MEDLINE, Embase, CINAHL, LILACS, DARE and two trial registries. We also checked the reference sections of relevant studies and contacted experts in the field for any additional trials. Randomised controlled trials comparing intentional endometrial injury before embryo transfer in women undergoing IVF, versus no intervention or a sham procedure. We used standard methodological procedures recommended by Cochrane. Two independent review authors screened studies, evaluated risk of bias and assessed the certainty of the evidence by using GRADE (Grading of Recommendation, Assessment, Development and Evaluation) criteria. We contacted and corresponded with study investigators as required. Due to the high risk of bias associated with many of the studies, the primary analyses of all review outcomes were restricted to studies at a low risk of bias for selection bias and other bias. Sensitivity analysis was then performed including all studies. The primary review outcomes were live birth and miscarriage. Endometrial injury versus control (no procedure or a sham procedure) A total of 37 studies (8786 women) were included in this comparison. Most studies performed endometrial injury by pipelle biopsy in the luteal phase of the cycle before the IVF cycle. The primary analysis was restricted to studies at low risk of bias, and included eight studies. The effect of endometrial injury on live birth is unclear as the result is consistent with no effect, or a small reduction, or an improvement (odds ratio (OR) 1.12, 95% confidence interval (CI) 0.98 to 1.28; participants = 4402; studies = 8; I2 = 15%, moderate-certainty evidence). This suggests that if the chance of live birth with IVF is usually 27%, then the chance when using endometrial injury would be somewhere between < 27% and 32%. Similarly, the effect of endometrial injury on clinical pregnancy is unclear (OR 1.08, 95% CI 0.95 to 1.23; participants = 4402; studies = 8; I2 = 0%, moderate-certainty evidence). This suggests that if the chance of clinical pregnancy from IVF is normally 32%, then the chance when using endometrial injury before IVF is between 31% and 37%. When all studies were included in the sensitivity analysis, we were unable to conduct meta-analysis for the outcomes of live birth and clinical pregnancy due to high risk of bias and statistical heterogeneity. Endometrial injury probably results in little to no difference in chance of miscarriage (OR 0.88, 95% CI 0.68 to 1.13; participants = 4402; studies = 8; I2 = 0%, moderate-certainty evidence), and this result was similar in the sensitivity analysis that included all studies. The result suggests that if the chance of miscarriage with IVF is usually 6.0%, then when using endometrial injury it would be somewhere between 4.2% and 6.8%. Endometrial injury was associated with mild to moderate pain (approximately 4 out of 10), and was generally associated with some minimal bleeding. The evidence was downgraded for imprecision due to wide confidence intervals and therefore all primary analyses were graded as moderate certainty. Higher versus lower degree of injury Only one small study was included in this comparison (participants = 129), which compared endometrial injury using two different instruments in the cycle prior to the IVF cycle: a pipelle catheter and a Shepard catheter. This trial was excluded from the primary analysis due to risk of bias. In the sensitivity analysis, all outcomes reported for this study were graded as very-low certainty due to risk of bias, and as such we were not able to interpret the study results. The effect of endometrial injury on live birth and clinical pregnancy among women undergoing IVF is unclear. The results of the meta-analyses are consistent with an increased chance, no effect and a small reduction in these outcomes. We are therefore uncertain whether endometrial injury improves the chance of live birth or clinical pregnancy in women undergoing IVF. Endometrial injury does not appear to affect the chance of miscarriage. It is a somewhat painful procedure associated with a small amount of bleeding. In conclusion, current evidence does not support the routine use of endometrial injury for women undergoing IVF.

Pregnancy outcomes following in vitro fertilization frozen embryo transfer (IVF-FET) with or without preimplantation genetic testing for aneuploidy (PGT-A) in women with recurrent pregnancy loss (RPL): a SART-CORS study.

Can preimplantation genetic testing for aneuploidy (PGT-A) improve the live birth rate in patients with recurrent pregnancy loss (RPL)? PGT-A use was associated with improved live birth rates in couples with recurrent pregnancy loss undergoing frozen embryo transfer (IVF-FET). Euploid embryo transfer is thought to optimize outcomes in some couples with infertility. There is insufficient evidence, however, supporting this approach to management of recurrent pregnancy loss. This study included data collected by the Society of Assisted Reproductive Technologies Clinical Outcomes Reporting System (SART-CORS) for IVF-FET cycles between years 2010 through 2016. A total of 12631 FET cycles in 10060 couples were included in this analysis designed to assess the utility of PGT-A in couples with RPL undergoing FET, including 4287 cycles in couples with tubal disease who formed a control group. The experimental group included couples with RPL (strictly defined as a history of 3 or more pregnancy losses) undergoing FET with or without PGT-A. The primary outcome was live birth rate. Secondary outcomes included rates of clinical pregnancy, spontaneous abortion, and biochemical pregnancy loss. Differences were analyzed using generalized estimating equations logistic regression models to account for multiple cycles per patient. Covariates included in the model were age, gravidity, geographic region, race/ethnicity, smoking history, and indication for assisted reproductive technologies. Analyses were stratified for age groups as defined by SART: <35 years, 35-37 years, 38-40 years, 41-42 years, and >42 years. In women with a diagnosis of RPL, the adjusted odds ratio (OR) comparing IVF-FET with PGT-A versus without PGT-A for live birth outcome was 1.31 (95% CI: 1.12, 1.52) for age <35 years, 1.45 (95% CI: 1.21, 1.75) for ages 35-37 years, 1.89 (95% CI: 1.56, 2.29) for ages 38-40, 2.62 (95% CI: 1.94-3.53) for ages 41-42, and 3.80 (95% CI: 2.52, 5.72) for ages >42 years. For clinical pregnancy, the OR was 1.26 (95% CI: 1.08, 1.48) for age <35 years, 1.37 (95% CI: 1.14, 1.64) for ages 35-37 years, 1.68 (95% CI: 1.40, 2.03) for ages 38-40 years, 2.19 (95% CI: 1.65, 2.90) for ages 41-42, and 2.31 (95% CI: 1.60, 3.32) for ages >42 years. Finally, for spontaneous abortion, the OR was 0.95 (95% CI: 0.74, 1.21) for age <35 years, 0.85 (95% CI: 0.65, 1.11) for ages 35-37 years, 0.81 (95% CI: 0.60, 1.08) for ages 38-40, 0.86 (95% CI: 0.58, 1.27) for ages 41-42, and 0.58 (95% CI: 0.32, 1.07) for ages >42 years. The retrospective collection of data including only women with recurrent pregnancy loss undergoing FET presents a limitation of this study, and results may not be generalizable to all couples with recurrent pregnancy loss. Also, data regarding evaluation and treatment for RPL for the included women is unavailable. This is the largest study to date assessing the utility of PGT-A in women with RPL. PGT-A was associated with improvement in live birth and clinical pregnancy in women with RPL, with the largest difference noted in the group of women with age greater than 42 years. Couples with RPL warrant counseling on all management options to reduce subsequent miscarriage, which may include IVF with PGT-A for euploid embryo selection. There are no conflicts of interest to declare. N/A.

Single oral dose of vitamin D3 supplementation prior to in vitro fertilization and embryo transfer in normal weight women: the SUNDRO randomized controlled trial

Improving invitro fertilization success is an unmet need. Observational studies have suggested that women with deficient or insufficient vitamin D have lower chances of invitro fertilization success, but whether supplementation improves clinical pregnancy rate remains unclear. This study aimed to determine whether oral vitamin D3 supplementation improves clinical pregnancy in women undergoing an invitro fertilization cycle. The "supplementation of vitamin D and reproductive outcome" trial is a 2-center randomized superiority double-blind placebo-controlled trial. Subjects were recruited between October 2016 and January 2019. Participants were women aged 18 to 39 years with low vitamin D (peripheral 25-hydroxyvitamin D of <30 ng/mL), serum calcium of ≥10.6 mg/dL, body mass index of 18 to 25 kg/m2, and antimüllerian hormone levels of >0.5 ng/mL and starting their first, second, or third treatment cycle of conventional invitro fertilization or intracytoplasmic sperm injection. The primary outcome was the cumulative clinical pregnancy rate per cycle. Pregnancies obtained with both fresh or frozen embryo transfers were included. Clinical pregnancy was defined as an intrauterine gestational sac with a viable fetus. The primary analysis was performed according to the intention-to-treat principle and could also include natural conceptions. Secondary outcomes included total dose of gonadotropins used, embryologic variables (number of oocytes retrieved, number of suitable oocytes retrieved, fertilization rate, and rate of top-quality embryos), and clinical outcomes (miscarriage rate and live birth rate). Overall, 630 women were randomized 2 to 12 weeks before the initiation of the invitro fertilization cycle to receive either a single dose of 600,000 IU of vitamin D3 (n=308) or placebo (n=322). Interestingly, 113 (37%) and 130 (40%) women achieved a clinical pregnancy in the treatment and placebo groups, respectively (P=.37). The risk ratio of clinical pregnancy in women receiving vitamin D3 was 0.91 (95% confidence interval, 0.75-1.11). Compared with the placebo, vitamin D3 supplementation did not improve the rate of clinical pregnancy. Exploratory subgroup analyses for body mass index, age, indication to invitro fertilization, ovarian reserve, interval between drug administration and initiation of the cycle, and basal levels of 25-hydroxyvitamin D failed to highlight any clinical situation that could benefit from the supplementation. In women with normal weight with preserved ovarian reserve and low vitamin D levels undergoing invitro fertilization cycles, a single oral dose of 600,000 IU of vitamin D3 did not improve the rate of clinical pregnancy. Although the findings do not support the use of vitamin D3 supplementation to improve invitro fertilization success rates, further studies are required to rule out milder but potentially interesting benefits and explore the effectiveness of alternative modalities of supplementation.

Correlation between Serum Anti-Müllerian Hormone Levels and Antral follicle count in prediction of clinical pregnancy in women with unexplained infertility undergoing ICSI cycles

Background: It is obvious that after years of publications worldwide. The question of whether the serum level of AMH predicts pregnancy after ICSI still unresolved. In the present study the correlation between serum AMH levels and pregnancy rate in a population of women undergoing their first ICSI cycle is investigated.Objective: We assess accuracy of serum anti-mullerian hormone levels and anti follicle count in prediction of clinical pregnancy in women with unexplained infertility and undergoing ICSI cycles. Patients and Methods: This is a retrospectively study in assisted reproductive technology unit at Maternity Hospital – Ain Shams University from August 2018 to June 2019. This study included 71 women with unexplained primary infertility in ART unit undergoing ICSI cycles. Simple random sampling. Results: we included (patients with unexplained primary infertility who underwent their first ICSI cycle aged 20-35 years with BMI ≤ 30 without associated medical problems as diabetes mellitus, hypertension and polycystic ovary. Serum AMH was measured within 3 months before the beginning of the ICSI cycle, ovarian stimulation was carried out, and all embryos transfer were carried out on a fresh cycle. Conclusion: In this study it was found that as the AMH level increases, the number of oocytes increases as well, but it is not a predictor of oocyte quality or pregnancy rate.

Effects of age on pregnancy outcomes in patients with simple tubal factor infertility receiving frozen-thawed embryo transfer

This study was to retrospectively analyze the effect of the age of embryos transfer and oocyte retrieval on the clinical pregnancy outcome in patients with simple tubal factor infertility (TFI) who received frozen-thawed embryo transfer. Patients (n = 3619) with simple TFI who underwent in vitro fertilization (IVF)/ intracytoplasmic sperm injection (ICSI) frozen-thawed embryo transfer at our hospital were enrolled. Univariate logistic regression analysis, categorical multivariate logistic regression analysis, curve fitting and threshold effect analysis were performed. Age of embryo transfer was a significant (P < 0.05) independent risk factor affecting the clinical pregnancy, live birth, and miscarriage rates. The Clinical pregnancy outcome declined significantly after the age of 34 years. After limiting the female oocyte retrieval age to ≤ 34 years, no significant change was detected in the clinical pregnancy, live birth, or miscarriage rate with increase of transplantation age. In conclusion, in patients with simple TFI undergoing IVF/ICSI frozen-thawed embryo transfer, age is a significant independent risk factor affecting the clinical pregnancy, live birth, and miscarriage rate. Aging of oocytes has a greater impact on the clinical pregnancy in women with simple TFI than the aging of the body. Patients with TFI can freeze embryos in advance to preserve fertility.

IVF/ICSI success rate in PCOD women in fresh IVF cycle

Polycystic ovary syndrome (PCOS) is a common endocrine disorder of women, which occurs in 5% to 13% in women of reproductive age. It is one of the major reason of infertility in women. Therefore, the prediction of clinical pregnancy in women with PCOS is more challenging. Our aim was to investigate the IVF/ICSI outcomes in PCOD patients. In the present retrospective study, total of 126 women in 133 fresh IVF cycles were involved, where 42 patient were PCOD and 84 patient were non-PCOD (other factor of infertility). All the patients’ medical data of age, duration of infertility, factor of infertility, AMH hormone level, number of total retrieved oocyte, matured (M2) oocytes, day 3 cleaved embryos and biochemical pregnancy rates were used for this study and data were statistically analyzed by Student T-Test. After statistical analysis, significantly higher AMH level, higher number of total oocyte, mature oocyte and day3 cleaved embryos were observed. The biochemical pregnancy rate was also found to be higher in PCOD patient but it was not statistically significantly. In the present study, number of oocytes and cleaved embryos were found to significantly higher in PCOD group but biochemical pregnancy was not significant.

The effect of administration of intravenous intralipid on pregnancy outcomes in women with implantation failure after IVF/ICSI with non-donor oocytes: A randomised controlled trial

ObjectiveDoes the administration of intravenous intralipid in women with previous implantation failure at the time of embryo transfer improve pregnancy outcomes in terms of biochemical pregnancy rate, clinical pregnancy rate, ongoing pregnancy rate, and ongoing pregnancy rate? Study DesignThis was a single blinded randomised controlled trial of 105 subjects with previous failed IVF undergoing self donor oocyte IVF/ICSI from January 2017 to May 2018. Randomisation was by computer generated sequence after oocyte pickup. Results were analysed for 102 women, excluding three women due to poor embryo quality. Women in the study arm(n = 52) received 2 doses of 20% intravenous intralipid (Fresenius Kabi), 4 ml diluted in 250 ml normal saline by slow infusion. The first dose was given immediately after oocyte recovery, and the second dose was given on the day of embryo transfer, 1 h prior to the transfer. The control group (n = 50) received normal saline. Flexible ovarian stimulation protocols were used. All the women received routine luteal phase support with micronised vaginal progesterone. Results102 women underwent analysis, 52 in the study group and 50 in control group. There was no significant difference in the baseline characteristics. There was a significant difference in the biochemical pregnancy rate in the intralipid group (40.38%) versus control (16%) [(p = 0.006), RR = 2.5 (1.23–5.16 CI)], clinical pregnancy rate [(34.62% vs 14%), p = 0.006, RR = 2.5(1.13–5.40 CI)], implantation rate [(16.6% vs 6.6%), p = 0.012, RR = 2.5(1.18 to 5.41 CI)], and take home baby rate [28.8% vs 10%, p = 0.024, RR = 2.8(1.1–7.3)]. The adjusted odds ratio for clinical pregnancy in women who received intralipid vs placebo was 3.1 (1.02–9.70 95% CI), p = 0.046. No adverse effects of intralipid were observed. ConclusionThis study shows a statistically significant increase in implantation rate and live birth rate in women who receive intravenous intralipid with prior implantation failure after IVF/ICSI. These findings concur with other studies; however, literature is limited. The effect of intralipid on the immunological abnormalities in women who experience recurrent implantation failure needs to be investigated further.

Effect of deflazacort on pregnancy outcome in kidney transplant patients: should we change the immunosuppressant before conception?

BackgroundDespite the good prognosis in patients with transplant organs, limited evidence is available on how immunosuppressants affect pregnancy. The aim of this study was to determine whether immunosuppressant use affects the pregnancy outcome and to identify whether there is any need to change the immunosuppressant before the patient tries to conceive.MethodsThis retrospective cohort study included women with previous kidney transplantation history who visited the Department of Obstetrics and Gynecology for either infertility or antenatal care between January 2005 and May 2016. A total of 40 cases (36 women) met the inclusion criteria. Statistical analyses were performed using SAS version 9.4.ResultsThere were no differences in the immunosuppressant regimen between the pregnant and non-pregnant groups (never-pregnant+miscarriage) (P = 0.73). Individual immunosuppressant use was significantly different in terms of pregnancy outcome among the never-pregnant, miscarriage, and clinical pregnancy groups (azathioprine, P = 0.01; deflazacort, P < 0.0001). Only deflazacort use differed significantly between the clinical pregnancy and non-pregnant groups (P = 0.003). After adjusting for factors that may affect pregnancy outcome, deflazacort use remained significantly associated with a decreased odds ratio for clinical pregnancy (P = 0.02). Cox regression analysis also showed that deflazacort use was the only remaining factor that could hinder the success of clinical pregnancy (P = 0.03).ConclusionsOur study suggests that the type of immunosuppressive regimen may not affect the success of clinical pregnancy. However, deflazacort may decrease the possibility of clinical pregnancy in women with kidney transplant when they try to conceive.